We performed two experiments on the effects of exogenous keratinocyte growth factor (KGF) on oviductal and vaginal epithelia. In Exp. 1, juvenile (1 year old) monkeys were injected with human KGF (5 mg/kg) or vehicle daily for 6 days. On treatment day 6, the monkeys were injected with Br-dU (50 mg/kg) and reproductive tracts were collected 1 hr later. In Exp. 2, juvenile monkeys were ovariectomized and treated sequentially with estradiol (E2 ) and progesterone (P) implants to induce menstrual cycles. During the test cycle, KGF (5 mg/kg) or vehicle was injected daily IV for 5 days, beginning 1 day before the P implant was withdrawn, with the E2 implant remaining in place. On day 4 of P withdrawal/E2 treatment the monkeys were injected with Br-d U (50 mg/kg) and tissues were collected 1 hr later. In Exp. 1, KGF substantially increased the number of epithelial cells incorporating Br-dU in both the oviduct and vagina (mean percent Br-dU-positive cells = oviduct 12.5% for KGF vs 0.8% for vehicle; vagina 13.6 % vs 1.3% for vehicle). In Exp. 2, E2 action alone (vehicle controls) stimulated proliferation in both the oviduct and vagina above the levels found in the untreated juveniles in Exp 1. Exogenous KGF significantly stimulated epithelial proliferation in the vagina (Br-dU positive cells = 18 q 4.5% for KGF and 6.1 q 0.13% for vehicle; P<0.05) but not in the oviduct (22 q 4.8 for KGF vs 17 q 1.9 for vehicle, NS). In summary, when KGF was administered in the absence of E2, both oviduct and vagina responded with increased proliferation. When KGF was administered in the presence of E2, the vaginal epithelium responded with enhanced proliferation, while the oviductal epithelium was refractory. These results indicate that the vagina may be a more sensitive organ in which to study mechanisms of KGF action.